Wang W, Smail N, Wang P, Chaudry I H
Center for Surgical Research, Brown University School of Medicine, Providence, Rhode Island 02903, USA.
J Surg Res. 1998 Sep;79(1):39-46. doi: 10.1006/jsre.1998.5385.
Although intestinal barrier failure after hemorrhage is a well-documented event, the underlying mechanism is poorly understood. The aim of this study, therefore, was to determine whether altered intestinal permeability after hemorrhage is associated with upregulation of local and systemic interleukin-6 (IL-6). To study this, rats underwent laparotomy (i.e., trauma induced) and were bled to and maintained at a mean arterial pressure of 40 mm Hg until 40% of the shed blood volume was returned in the form of Ringer's lactate. The animals were then resuscitated with four times the volume of shed blood with Ringer's lactate over 60 min. At 1.5 h postresuscitation, an in vivo ligated loop of a distal small intestine was formed and the passage of 4-kDa fluorescein isothiocyanate-conjugated dextran (FD4) from the intestinal lumen into the portal vein and carotid artery blood was analyzed by fluorescence spectrometry. Samples from the portal vein and a carotid artery were collected and plasma IL-6 was assayed. Intraepithelial lymphocytes from a distal small intestine were isolated and cultured in vitro for 24 h with or without anti-rat CD3 monoclonal antibody stimulation. IL-6 activity in freshly isolated cells and its release by cultured lymphocytes were determined. Intestinal perfusion and portal blood flow were determined by radioactive microspheres in another set of parallel experiments. The results indicate that lumen-to-blood passage of FD4 through the wall of the small intestine increased significantly at 1.5 h after hemorrhage and resuscitation and was associated with decreased intestinal perfusion and portal blood flow. Plasma IL-6 levels in the portal vein and carotid artery markedly increased at 1.5 h after hemorrhage and resuscitation. In addition, a significant correlation was observed between plasma IL-6 and FD4 concentrations. Higher IL-6 activity in freshly isolated cells was found in hemorrhaged rats. Increased IL-6 release by cultured lymphocytes was also observed either with or without anti-rat CD3 monoclonal antibody stimulation. Thus, the increased intestinal permeability following trauma-hemorrhage and resuscitation appears to be associated with systemic and intestinal IL-6 upregulation.
尽管出血后肠屏障功能衰竭是一个有充分文献记载的现象，但其潜在机制仍知之甚少。因此，本研究的目的是确定出血后肠道通透性改变是否与局部和全身白细胞介素-6（IL-6）上调有关。为了研究这一点，对大鼠进行剖腹手术（即诱导创伤），放血至平均动脉压为40 mmHg并维持该水平，直到40%的失血量以乳酸林格液的形式回输。然后在60分钟内用四倍失血量的乳酸林格液对动物进行复苏。复苏后1.5小时，在远端小肠形成体内结扎肠袢，通过荧光光谱法分析4 kDa异硫氰酸荧光素偶联葡聚糖（FD4）从肠腔进入门静脉和颈动脉血的情况。采集门静脉和颈动脉样本并检测血浆IL-6。从远端小肠分离上皮内淋巴细胞，在有或无抗大鼠CD3单克隆抗体刺激的情况下体外培养24小时。测定新鲜分离细胞中的IL-6活性及其在培养淋巴细胞中的释放量。在另一组平行实验中，用放射性微球测定肠道灌注和门静脉血流量。结果表明，出血和复苏后1.5小时，FD4从小肠壁的肠腔到血液的通过率显著增加，且与肠道灌注和门静脉血流量减少有关。出血和复苏后1.5小时，门静脉和颈动脉中的血浆IL-6水平显著升高。此外，观察到血浆IL-6与FD4浓度之间存在显著相关性。在出血大鼠中发现新鲜分离细胞中的IL-6活性较高。在有或无抗大鼠CD3单克隆抗体刺激的情况下，均观察到培养淋巴细胞释放的IL-6增加。因此，创伤性出血和复苏后肠道通透性增加似乎与全身和肠道IL-6上调有关。
